The first steps in the metabolic degradation of hyaluronic acid and chondroitin sulfate, in man, are mediated by the enzyme hyaluronidase. These glycosaminoglycans, along with keratan sulfate, are the major polysaccharide components of the articular cartilage and synovial fluid of joint tissue. Various high charge density macromolecules are able to affect the rate of hyaluronidase activity. The enzyme can also be inhibited by a component of synovial fluid and cartilage. Objectives of this proposal include: purification and analysis of hyaluronidase from human synovial fluid, examination of the effects of high charge density macromolecules on the enzyme, and elucidation of the biochemical and physical properties of the endogenous enzyme inhibitors present in joint tissue. These studies should establish the physiological role of lysosomal hyaluronidase in articular tissue as well as its involvement in the alterations observed in the joints of individuals with osteoarthritis and rheumatoid arthritis. This could lead to new therapeutic measures for treating the symptoms of these diseases.